| Autor: |
Owen, S.M., Rudolph, D., Wang, W., Cole, A.M., Sherman, M.A., Waring, A.J., R.I. Lehrer, Lal, R.B. |
| Předmět: |
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| Zdroj: |
Journal of Peptide Research; Jun2004, Vol. 63 Issue 6, p469-476, 8p |
| Abstrakt: |
The ability of certain θ-defensins, including retrocyclin-1, to protect human cells from infection by HIV-1 marks them as potentially useful molecules. θ-Defensins composed of l-amino acids are likely to be unstable in environments that contain host and microbial proteases. This study compared the properties of two enantiomeric θ-defensins, retrocyclin-1, and RC-112. Although these peptides have identical sequences, RC-112 is composed exclusively of d-amino acids, whereas retrocyclin-1 contains only l-amino acids. We compared the ability of these peptides to protect JC53-BL human cells from infection by 30 primary HIV-1 isolates. JC53-BL cells are modified HeLa cells that express surface CD4, CXCR4, and CCR5. They also contain reporter cassettes that are driven by the HIV-1 LTR, and express β-galactosidase and luciferase. The HIV-1 isolates varied in co-receptor specificity and included subtypes A, B, C, D, CRF01-AE, and G. RC-112 was several fold more potent than retrocyclin-1 across the entire HIV-1 panel. Although RC-112 bound immobilized gp120 and CD4 with lower affinity than did retrocyclin-1, surface plasmon resonance experiments performed with 1 μg/mL of RC-112 and retrocyclin-1 revealed that both glycoproteins were bound to a similar extent. The superior antiviral performance of RC-112 most likely reflected its resistance to degradation by surface-associated or secreted proteases of the JC53-BL target cells. θ-Defensins composed exclusively of d-amino acids merit consideration as starting points for designing microbicides for topical application to the vagina or rectum. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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